Automation of Cell Banking & Characterisation Pathways at the UKSCB: Underpinning Delivery of a Core Component of the UK Infrastructure for Regen Med

The proposal is for capital funding to provide equipment and facilities for improving the banking and characterisation of pluripotent stem cells provided by the UK Stem Cell Bank as seed stocks for research and clinical applications. The automation of key processes in the banking, characterisation and quality control of stem cell lines, intended as starting materials for research and development of cellular therapies, will generate significant improvements in the speed and quality of cell banking and testing. These increased efficiencies will be focused mainly in the area of staff "contact time" where automation of some banking functions and reduction in sample preparation time for QC and research will free up significant staff time for enhanced characterisation of clinical seed stocks. This streamlining will result in improved quality and consistency of cell products: minimising process variability and enhancing robustness and reliability. It will also enhance the Bank's ability to conduct underpinning development work on key safety characteristics which will define the suitability of cell lines used for therapy, such as studies of genetic stability and maintenance of phenotype and function after banking and extended in vitro culture. This information will be essential for the utility of these cells for cell-based medicines. It will also enable the Bank to provide further support to the clinical and manufacturing communities in the development of both clinical hESC and hiPSC lines. The equipment will also be used in the numerous current and proposed collaborations with academic, regulatory, SME and pharmaceutical partners, in which the UKSCB is providing support to facilitate regulatory approval of commercial products.

The equipment included in the bid falls into two areas: 1. Equipment for automating aspects of cell banking; 2. Equipment intended to streamline or enhance the quality control and underpinning research in the area of stem cell characterisation and safety testing. Details of the equipment requested are given in the Case for Support.
1. In considering the requirements of the Bank for automation we have considered the role that the UKSCB will play in the development of regenerative medicine in the UK and the transit of NIBSC into the MHRA. In response to potential CoIs, the Bank has moved away from the provision of large clinical trials stocks, toward the provision of seed stocks for clinical application. Scale-up, to produce large banks of cells through fully-automated systems are not warranted for the size of banks the UKSCB intends to produce in the future. The need is for flexibility, in terms of size and number of cell lines produced at any given time and the ability to respond rapidly to the provision of cell banks for hESC and hiPSC research collaborations of the kind already undertaken by the Bank.
2. Automation, to enhance our ability to increase the throughput of samples for QC testing and research, is another facet of this bid. There is a need to provide robust and enhanced assays for genomic and global transcriptomic profiling of cell banks. Microarray technology provides a first-line analysis method that allows for cost-effective acquisition of comprehensive cell genotype and gene expression data. Further analysis and validation of array data can then be performed by sequencing and real time PCR using current facilities at NIBSC. These technologies, in conjunction with a microarray platform, would allow for a seamless workflow from global profiling to targeted confirmation. Acquired genomic and transcriptomic data will be complied to form a reference database for the UKSCB user community for the UKSCB cell lines.

The capital bid will enhance the safety and efficacy of seed stocks of stem cells used for downstream clinical therapies. The primary beneficiaries of the UKSCB's enhanced capabilities to bank and characterises pluripotent stem cells will be the basic and clinical stem cell research sectors, including companies engaged in developing and manufacturing future regenerative medicines based on human ES and iPS cells. The bid represents a targeted programme of automation for key aspects of banking and testing of stem cell lines to increase the capacity of the UKSCB as the UK's national facility for the supply of clinical grade hPSC lines for the development of patient therapies. It will enhance the genomic and phenotypic characterisation of UK stem cell lines to ensure that they are safe and fit for purpose. This will enable the UKSCB to better meet its commitments as part of a coordinated UK infrastructure for regenerative medicine and enable the UKSCB to sustain its internationally recognised expertise. The benefits to the stem cell community would be three-fold. Firstly, improved seed stocks of clinical utility with enhanced cell characterisation and QC testing would be provided by the Bank to the user community. Secondly, the knowledge gained in automating banking processes would provide a valuable insight to UK regulators on potential downstream issues in the development of cellular therapies. Finally, the enhanced capacity that the capital bid provides, will be made available to the UK hPSC-user community through current and future relationships with an expanded range of academic, health service and industrial partners in a broad range of cell therapy applications. The equipment identified in this bid will contribute to improving quality standards and comparability, provide rapid in-process QC testing and contribute to biological standardisation and the investigation of key safety issues such as adventitious agents and studies on genetic stability and maintenance of phenotype and function after banking and extended in vitro culture. The quality controlled cell banks and the enhanced characterisation data will enable the Bank to provide further support to the clinical and manufacturing communities in the development of both clinical hESC and hiPSC lines and help the UK to consolidate and expand its international position in cell therapy. The acquired genomic and transcriptomic data will be made available through the UKSCB website, in the form of a reference database for the UKSCB user community, to compliment the provision of seed stocks to the academic and commercial sectors , thus strengthening the Bank's supportive role within both UK and international stem cell research. This will impact significantly on the Regenerative Medicine sector as such data will provide baseline comparators for ongoing research and downstream cell banks used at the starting point for cellular therapies. The equipment will also be used in the numerous current and proposed collaborations with academic, regulatory, SME and pharmaceutical partners, in which the UKSCB is providing support to facilitate regulatory approval of commercial products.